Abstract

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, with complicated pathological mechanism and extremely high prevalence and fatality rate. In this study, we investigated the role of METRNL in sepsis-induced renal injury and to identify potential downstream molecules. Male C57BL/6 mice were subjected to laparotomy followed by extracorporeal cecum mobilization and ligation as vivo model. THP-1 cells were stimulated with LPS as vitro model. As compared to the normal tissue or normal serum samples, the tissue and serum of METRNL expression levels in sepsis-induced renal injury were reduced. METRNL protein reduced inflammation and inhibited renal injury in sepsis mice model. METRNL up-regulation inhibited inflammation in vitro model. The inhibition of METRNL promoted inflammation and renal injury in sepsis mice model. METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways. In conclusion, we are the first to identify METRNL as a co-activator of PPARδ to inhibit inflammation in sepsis-induced renal injury and potentiate the activity target of renal injury.

Highlights

  • Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, with complicated pathological mechanism and extremely high prevalence and fatality rate (Nadeem et al, 2021; Ma et al, 2019)

  • To observe the function of METRNL on inflammation in sepsis-induced renal injury, we used reorganized METRNL protein to inject into mice with sepsis

  • In order to verify the effects of METRNL on inflammation in vitro model, METRNL plasmid induced METRNL expression, reduced TNF-α, IL-1β, IL-6 and IL-4 levels, and increased IL10 levels in vitro model of sepsis (Figure 4A-F)

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Summary

Introduction

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, with complicated pathological mechanism and extremely high prevalence and fatality rate (Nadeem et al, 2021; Ma et al, 2019). Sepsis is easy to develop into septic shock and multiple organ dysfunction syndrome (MODS), which is life-threatening (Nadeem et al, 2021; Ma et al, 2019). Acute kidney injury (AKI) pathologically characterized by progressively declined renal function is a common complication of sepsis (Wang et al, 2021). Epidemiological studies have shown that approximately 40% of patients with sepsis will develop AKI (Yoo et al, 2020). A lack of effective prognostic evaluation indicators is one of the main causes for the high mortality rate of AKI (Liu et al, 2020)

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